Changes in the Uterus and Vagina of Mice Treated Neonatally with Antiestrogens

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Abstract
Adenosis-like lesions (ADL) were found in the upper vagina including the cervical region of ICR mice as early as 1 day after 5 daily injections of 200 µg tamoxifen (Tx) starting on the day of birth (200-µgTx mice). ADL developed progressively from 5 to 30 days of age. Involution of the musculature and suppression of the gland genesis occurred in the uterus of 5- to 30-day-old 200-µg Tx mice. The uterine abnormality resulted in a loss of type III collagen and laminin, and in an increase in fibronectin and type I collagen in the mesenchymal stroma of 15-day-old, 200-µg Tx mice. Vaginal ADL and uterine myometrial involution were also encountered in 35-day-old mice given neonatal injections of 2–200 µg Tx 200 µg clomiphene (Qm) and 200 µg naf oxidine (Naf) respectively. These changes were never observed in control and 0.2-µg Tx mice. Ovariectomy performed at 10 days resulted in a reduction in the weight of uteri and the extent of ADL occupancy in Tx, Clm and Naf mice. Five daily injections of 0.1 µg 17β-estradiol (F¾) beginning at 30 days of age increased uterine weight and ADL occupancy extent in Tx (2–200 µg) Clm and Naf mice. The present findings suggest, therefore, that the antiestrogens act as an estrogen agonist to mouse uterus and vagina and that the induced ADL develops progressively depending on ovarian estrogen.

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